期刊
BIOMOLECULES
卷 12, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biom12060778
关键词
trichothecene; apoptosis; cell cycle arrest; mitochondrial pathway; anti-tumor
资金
- Outstanding Youth Foundation of Hei-Long-Jiang province
The study investigated the secondary metabolites of the endophytic fungus Fusarium sporotrichioides isolated from Rauvolfia yunnanensis Tsiang, which has anti-tumor activity. It identified five trichothecenes, including a previously undescribed metabolite. Surprisingly, 8-n-butyrylneosolaniol (3) showed stronger anti-tumor activity than T-2 toxin and promoted apoptosis in Huh-7 cells.
The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC50 value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents.
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